Source:http://linkedlifedata.com/resource/pubmed/id/20846942
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
|
| pubmed:dateCreated |
2010-11-5
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| pubmed:abstractText |
Interferon regulatory factor-1 (IRF-1), a transcription regulator involved both in inducing and in mediating the effects of interferon, is encoded by a highly polymorphic gene in different ethnic populations. Some of these genetic variations have been described to be associated to disease traits in hepatitis C virus and in human immunodeficiency virus infection, including one single-nucleotide polymorphism rs2549009 within the promoter region. This study aimed at investigating the functional relevance of rs2549009 on IRF-1 transcriptional activity in peripheral blood mononuclear cells in its natural genomic environment. Haplotype-specific chromatin immunoprecipitation using antibodies directed against both the transcriptionally inactive and active RNA polymerase II (RNAPII) and allele-specific transcript quantification techniques were applied to ex vivo-derived samples from healthy heterozygous donors. Inactive serine 5 phosphorylated RNAPII was found to be preferentially bound to the rs2549009 A allele in all donors investigated. Active serine 2 phosphorylated (ser2-P) RNAPII, in contrast, was found to be precipitable, depending on the donor, preferentially either with the A or the G promoter variants or without any preference. The ratio of rs2549009 A/G promoter variants engaged by ser2-P RNAPII was closely related to the relative frequency of the respective IRF-1 transcripts, and relative allelic expression was found to be associated to total IRF-1 gene expression. These results provide evidence for a bidirectional IRF-1 gene expression imbalance that appears not to be solely controlled by rs2549009 in cis and may rely on a yet unidentified variant or haplotype or on environmental control in trans.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
1460-2083
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
19
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4587-94
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| pubmed:meshHeading |
pubmed-meshheading:20846942-Adult,
pubmed-meshheading:20846942-Alleles,
pubmed-meshheading:20846942-Chromatin Immunoprecipitation,
pubmed-meshheading:20846942-Female,
pubmed-meshheading:20846942-Gene Expression,
pubmed-meshheading:20846942-Genetic Variation,
pubmed-meshheading:20846942-Haplotypes,
pubmed-meshheading:20846942-Humans,
pubmed-meshheading:20846942-Interferon Regulatory Factor-1,
pubmed-meshheading:20846942-Leukocytes, Mononuclear,
pubmed-meshheading:20846942-Male,
pubmed-meshheading:20846942-Middle Aged,
pubmed-meshheading:20846942-Phosphoserine,
pubmed-meshheading:20846942-Polymerase Chain Reaction,
pubmed-meshheading:20846942-Polymorphism, Single Nucleotide,
pubmed-meshheading:20846942-Promoter Regions, Genetic,
pubmed-meshheading:20846942-RNA Polymerase II,
pubmed-meshheading:20846942-Regulatory Elements, Transcriptional,
pubmed-meshheading:20846942-Transcription, Genetic
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Functional relevance of the IRF-1 promoter polymorphism rs2549009 on transcriptional activity in a native genomic environment.
|
| pubmed:affiliation |
Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Georg-August-Universitaet, Robert-Koch-Strasse 40, Goettingen, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|